Preparation of aromatic organozinc compounds and composition therefore

ABSTRACT

The invention relates to a technique for preparing aromatic organozinc compounds and to a composition therefore. This composition constitutes a reactant that can be used to carry out the synthesis of organozinc compounds, and comprises a cobalt salt, a zinc salt, a polar aprotic solvent and elemental zinc in divided form, the elemental zinc being in solid form, the other elements being in a form dissolved in the solvent. Application to organic synthesis.

This application is an application under 35 U.S.C. Section 371 ofInternational Application Number PCT/FR02/02319 filed on Jul. 3, 2002.

The subject of the present invention is a novel method of synthesizingaryl organozinc derivatives. It relates more particularly to thesynthesis of aryl organozinc derivatives by a chemical route in thecatalytic presence of the element cobalt.

The reactivity of organozinc compounds, especially aryl organozinccompounds, has many specific features that make them particularly usefulin many organic synthesis operations. However, they are difficult toobtain and are often prepared from organometallic compounds producedwith more electronegative, that is to say more reducing, metals.

Furthermore, most of the techniques require the use of highly aprotic,and especially very dry, media.

Important advances have been recently made by the same authors as thoseof the present application, which advances have formed the subject ofthe patent application published by virtue of the patent cooperationtreaty under number WO 01/02625 A1. The technique described in thatpatent proposes an electrolytic synthesis in the presence of zinc saltsand in the presence of cobalt salts. The cathodic reduction of thesystem results in the synthesis of organozinc compounds with goodcoulumbic yields. This technique is also very versatile. In thistechnique, metallic zinc possibly present at the anode acts only as asource of zinc salt, the reaction taking place at the cathode.

However, this technique has the drawbacks associated with anyelectrolysis.

Thus, it is relatively expensive to implement such a technique, and anelectrolytic technique can be applied only to expensive products.

Another problem lies in the difficulty in producing large amounts insmall volumes by electrolytic techniques.

One of the objectives of the present invention is therefore to provide amethod for obtaining organozinc derivatives with good yields, bothreaction and conversion yields, and to do so without using anelectrolytic technique. These objectives, and others that will appearlater, are achieved by the use of cobalt as catalyst for the reactionbetween metallic zinc and an aryl halogen, and to do so without anelectrolysis device.

Thus the particle, or fragment taken in its entirety, of zinc is notconnected to any external electrolytic system, that is to say one inwhich the current source is located outside the reaction mixture, whichtherefore does not have the right to be called an “electrolytic bath”and does not act as anode. The formation of an organozinc compound maybe termed chemical formation as no apparent current can be detected.

It will be assumed that one day an electrochemical mechanism will beassigned to this reaction; the same parcel of metal will then act at thesame time as cathode and as anode.

This chemical nature of the reaction is demonstrated by the divided formof the introduction of the metal—the zinc is introduced in divided form,for example powder, machining chips, shot, etc. and is brought intocontact with no current source. There is no electrical connectionbetween the zinc and a current source external to the medium, which isconsequently not an “electrolytic” medium but simply a reaction mixture.

Over the course of the study that led to the present invention, it wasshown that it is preferable to avoid the use of good cobalt complexingagents, and especially bidentate complexing agents such as bipyridyls.Pyridine itself considerably slows down the reaction, favoring sidereactions.

On the other hand, light complexing agents, such as nitrile and possiblydinitrile functional groups, seem to favor the reaction.

Thus, according to the present invention, it is preferable that thecomplexing agents of pyridinic type be less than two times, preferablyless than one times, the amount expressed in moles of cobalt salts.

It is desirable for the same rules to apply to the strong cobaltcomplexing agents, such as optimally bidentate amines and phosphines.

This rule may be expressed in the following manner: the high molar ratioof cobalt to coordinating ligand, chosen from pyridines, phosphines andamines, is greater than 0.5, advantageously equal to 1 and preferably 2.

When a complexant is multidentate, the above rule will apply using theequivalents of complexing function and not the number of moles ofcomplexing product function.

It has also been shown that the presence of an aryl halide canpotentialize the reaction, especially when the ring carrying the X ofsaid ArX is at least as rich in electrons as a phenyl. Thispotentialization is most particularly effected by means of aryl halidesof a ring less rich in electrons than that of ArX, the zinc compound ofwhich it is desired to produce.

To evaluate the electron richness of a ring, reference may be made tothe Hammett constants taking as reference the Hammett constant σ_(p).This catalysis of the zinc by cobalt is surprizing insofar as, usually,zinc is capable of reducing in metallic form, by a technique sometimescalled cementation, the element cobalt, which is less reducing thanzinc.

According to another aspect of the invention, it has also been shownthat the presence of acid, advantageously an organosoluble acid,significantly improves the yields.

These acids may especially be carboxylic acids, fatty acids orhalogenated, and even perhalogenated, acids. Perfluorinated acids are ofparticular interest because of their solubility in organic phases and oftheir relatively high acidity.

Without this explanation being limiting, it is plausible that the roleof these acids is to depassivate the zinc used. The solvents used arepreferably solvents of the polar aprotic type, and especially thosewhose donor number is at least equal to 10 and preferably at most equalto 30, advantageously between 20 and 30, the limits being inclusive.

Said donor number corresponds to the ΔH (change in enthalpy) expressedin kilocalories per mole of the combination of said polar aproticsolvent with antimony pentachloride. This is described more precisely inthe work by Christian Reichardt: “Solvents and solvent effects inorganic chemistry” VCH, page 19, 1988. On this page is found thedefinition of the donor number.

With the exception of the particular case of nitrites, it is preferablefor the donor character to be due neither to the nitrogen nor to thephosphorus, but instead due to oxygen.

In the case of solvents with amide functional group, it will be assumedthat the donor aspect is due to the oxygen linked by a double bond tothe carbon of the amide functional group. Thus, amides form part of thesolvents capable of giving good results in the case of the reactionaccording to the invention.

The solvent must be sufficiently polar to dissolve the metals, or moreprecisely the salts of the metals used, and must be sufficientlylipophilic to at least partly dissolve the substrates of which it isdesired to form the organozinc compound. It is preferable to usesolvents that are sufficiently scarcely acidic (it is desirable fortheir pKa to be at least equal to 16, advantageously at least equal to20 and preferably at least equal to 25) for the reactions with hydrogento be as scarcely pronounced as possible. Thus, primary alcohols are tooacidic to give good results.

If there is need for acidity, it is then necessary to control its amountusing the acids that were mentioned above, and especially carboxylicacids such as trifluoroacetic acid and acetic acid itself. Fatty acidsmay also be used, whether or not they are perhalogenated (in generalperfluorentated) on the carbon carrying the carboxylic functional group.

Returning to the solvents, it will be preferable more specifically touse what are called polar aprotic solvents such as, for example, bythemselves or as a mixture:

-   -   purely oxygen-type solvents, particularly ethers, preferably        polyethers such as 1,2-dimethoxy ethane, or cyclic ethers such        as THF or dioxane;    -   amides or ureas (DMF, N-methyl-2-pyrrolidone, imidazolidone,        tetramethylurea, dimethoxypropylene, etc.);    -   sulfones (for example sulfolane) or sulfoxides (such as DMSO).        However, it will then be necessary, in these cases too, to check        that the zinc is not able, under the reaction conditions, to        reduce these solvents;    -   compounds with a nitrile functional group (for those that are        preferred, see below); and    -   nitriles; in order to be used these must preferably be liquid at        the reaction temperature (as goes without saying), but        polynitriles may also be used, and especially bis-nitriles.        These bis-nitriles are of particular interest because they are        scarcely complexing. They may be used as solvent, cosolvent or        light complexing agent, without lowering the yield.

It is desirable, in order to avoid the medium becoming too acidic, forthe bis-nitriles, that constitute the solvent, part of the solvent orthe coordinate, to be such that two nitrile functional groups areseparated by at least two carbons, advantageously by three carbons, viathe most direct path.

Dinitriloalkylenes whose alkylene group contains from 2 to 8 carbonatoms give good results. Mention may be made in particular ofglutaronitrile, methylglutaronitrile, adiponitrile, pimelonitrile andsuberonitrile.

The cobalt may be introduced into the reaction mixture in various waysand above all in various forms, but it is preferable for it to beintroduced in the form of a salt, preferably a cobaltous salt. Cobalticsalts may also be used, but they will cause additional consumption ofzinc.

To be effective, it is desirable for the cobalt to be present in aminimum concentration, at least equal to 10⁻³M. To be economic, it ispreferable for the cobalt not to be too concentrated—therefore thecobalt content is at most equal to 0.2 M. It has been shown during thepresent study that zinc salts can be useful at start-up of the reaction.It is therefore preferable to add zinc salts to the initial reactionmixture. These zinc salts may be any kind of salt, but it is often morepractical to introduce them in the form of a halide, and especially ofthe halide corresponding to the halides of the substrates of which it isdesired to form the organozinc compound.

The same applies to cobalt. However, it is necessary to avoid amultiplicity of anions in the mixture in order to be able more easily totreat the reaction solutions.

There is no clear-cut maximum amount of zinc salts to be used, but it ispreferable to arrange for the zinc salt, after the end of the reaction,not to exceed the solubility of said zinc salt in the media.

It is possible to dispense with a zinc salt, but the reaction, in allcases in its starts, will become autocatalytic, the zinc salts beingformed during the reaction. It is thus preferable to have a zinc saltconcentration of at least 10⁻³M, preferably at least 10⁻²M.

Aryl halides, that potentialize or act as adjuvant for the reaction, areespecially denoted in the examples by Ar′X′, where X′ represents thehalide in question. The amounts of adjuvant halide (Ar′X′) may be verylow, but it is preferable for them to be at least equal to 10⁻³M. It isalso preferable for its concentration to be at most equal to, and evenless than, that of the cobalt expressed in moles per liter. This isbecause if it is greater than that of cobalt, organozinc compounds ofthe adjuvant are present that may constitute an impurity with regard tothe desired organozinc compound. X′ may take the same values as X(especially chlorine, bromine, iodine), but ordinarily X′ is chosen tobe equal to X.

When Ar′X′ remains less than the amount of cobalt present (expressed inmoles per liter), the possible intermediate organozinc compound isessentially converted into a hydrogenated derivative corresponding tothe adjuvant aryl halide.

When the adjuvant aryl halide is such that the halogen is close (in theortho or equivalent position) to a functional group that complexes, evenweakly, cobalt, the organozinc compound corresponding to Ar′X may form,which may be problematic during synthesis. In general therefore, theyare not used as adjuvant aromatic halide.

On the other hand, such compounds may, without an adjuvant aromatic, beeasily converted into organozinc compounds.

The acid concentration is advantageously at least equal to 10⁻³M,advantageously 5×10⁻³M. The upper value is essentially limited by theamount of metallic zinc in the medium. The amount of acid must be lessthan that needed to dissolve all of the metallic zinc and leave enoughmetallic zinc for the reaction.

According to the present invention, it is possible to replace in theequivalent amounts (expressed in moles) by iodine (I₂).

In general, whether iodine or acids, it is preferable to be at arelatively low level in order to avoid spurious reactions, especiallythe formation of hydrocarbon instead of the desired organozinc compound.In general therefore, amounts of acid or of iodine of less than 10%,advantageously at most equal to 5%, for the aromatic constituting theprecursor substrate of the organozinc compound expressed in moles areused.

The concentration of an ArX to be converted into a zinc compound, whereX represents the halide or pseudohalide of said aryl (pseudo)halide andwhere Ar represents the aromatic residue, is not critical. However, itis preferable to be in a concentration range lying between 10⁻²M and 2M, preferably between 2×10⁻²M and 1.5M.

The pressure is virtually of no importance in the reaction.

On the other hand, the temperature may be a factor in reducing theyield; in particular, it is preferable to have the temperature as low aspossible, in general between the melting point of the reaction mixtureat 100° C., advantageously at a temperature of at most 80° C. and evenat most 50° C.

When the reaction rate is high enough, it is advantageous for thetemperature to be close to room temperature, and even 0° C.

The substrates (ArX) that can be converted into organozinc compounds bythe present invention represent a broad range of compounds. In general,the halides are halides corresponding to the relatively heavy halogens,that is to say to the halogens heavier than fluorine.

It may also be pointed out that, when the halogen (X) is linked to anaromatic ring depleted in electrons, it is preferable to use bromine orchlorine as halogen, chlorine being reserved for rings that areparticularly depleted in electrons. If the condition is fulfilled bysix-membered heterocycles, in the case of homocyclic aryl compounds, inorder to use a chlorine it is preferable for the sum of the Hammettconstants σ_(p) of the substituents (not taking into account the leavinghalide) to be at least equal to 0.40, preferably at least equal to 0.50.In contrast, rings that are particularly rich in electrons may useiodine as halide.

For more details about Hammett constants, the reader may refer to the3^(rd) edition of the manual written by Professor Jerry March “AdvancedOrganic Chemistry” (pages 242 to 250) published by John Wiley and Sons.

The substrates (ArX) having, as aromatic ring carrying X, five-memberedheterocycles, which include a chalcogen (such as furan and thiophene) asheteroatom, exhibit high convertibility into zinc compound, showexceptional reactivity and are always easily convertible into zinccompound.

The electron depletion of the ring may be due either to the presence ofelectron-withdrawing groups as substituents or, in the case ofsix-membered rings, by the replacement of a carbon with a heteroatom. Inother words, the electron-depleted ring may be a six-memberedheterocyclic ring, especially heterocyclic rings having an atom from thenitrogen column, and more particularly nitrogen.

Among electron-withdrawing groups giving good results, mention should bemade of acyl groups, nitrile groups, sulfone groups, carboxylate groups,trifluoromethyl groups or, more generally, perfluoroalkyl groups andhalogens of lower rank than the halide that will be converted into anorganozinc compound. When the substituents are halogens of the samerank, a diorganozinc compound is generally formed.

Among donor groups, that is to say those giving mediocre results withchlorine but good results with bromine, mention may be made of alkyloxylgroups, alkyl groups and amine and dialkylamine groups.

The aromatic derivative, namely the substrate of the present method,advantageously satisfies the following formula:

where:

-   -   Z represents a trivalent —C(R₁)=link, an atom of Column V,        advantageously a nitrogen;    -   X represents the leaving halogen; and    -   A represents either a link chosen either from ZH groups or from        chalcogens, advantageously of a rank at least equal to that of        sulfur, or from two-membered divalent unsaturated groups        CR₂=CR₃, N=CR₂ or CR₂=N.

If they are carried by adjacent atoms, two of the radicals R, R₁, R₂ andR₃ may be linked to form rings.

Thus the aryl groups may in particular be chosen from the followingformulae:

where Z₁ is chosen from the same meanings as those given for Z.

The radicals R₁, R₂, R₃ are chosen from the abovementioned substituentsand especially:

-   -   electron-withdrawing groups, in particular acyl groups, nitrile        groups, sulfone groups, carboxylate groups, trifluoromethyl        groups or, more generally, perfluoroalkyl groups and halogens of        lower rank than the halide that will be converted into an        organozinc compound;    -   donor groups, especially aryloxyl and alkyloxyl groups,        hydrocarbyl groups, such as aryl and alkyl (the latter word        being taken in its etymological sense) and amine groups,        including those that are monosubstituted and disubstituted with        alkylamine hydrocarbon groups.

It is desirable for the substrates to have at most 50 carbon atoms,advantageously at most 30 carbon atoms and preferably at most 20 carbonatoms.

Among the substrates that are particularly useful are aryl halides,preferably aryl chlorides, or more particularly aryl bromides,especially those carrying, in the meta position, an aliphatic (i.e. sp³)carbon carrying at least two fluorines, for example trifluoromethylarylhalides, preferably trifluoromethylaryl chlorides.

This method of synthesizing organozinc compounds may be extended, on theone hand, to all those in which the organozinc groups are linked tosp²-hybridized carbon atoms and especially to the synthesis oforganozinc compounds from vinyl halides, most particularly when theseare conjugated with aromatic rings. In general, the substrate is addedlast to the reaction mixture.

Another subject of the present invention is a composition forming areactant that can be used to carry out the synthesis of organozinccompounds, characterized in that it comprises a cobalt salt, a zincsalt, a polar aprotic solvent and elemental zinc in divided form, theelemental zinc being in solid form, the other elements being in a formdissolved in the solvent. This composition furthermore includes an acidor molecular iodine.

The constituents of the reactant may be added in various orders ofaddition.

According to a standard but nonobligatory method of implementation, thesalts used (cobalt salt, if this is provided, zinc salt and optionallyother salts), the adjuvants (such as iodine or acid) for activating themetallic zinc and the optional Ar′X′ (or the ArX, or a portion of ArX,when there is no Ar′X′) are introduced into the solvent, followedsecondly by the zinc and finally by the ArX (when there is an Ar′X′, orwhen all of the ArX has not yet been introduced).

As teaching, through the example (paradigm), the reader may refer to thegeneral experimental conditions that give an order of introduction ofthe components of the reactant. These general operating conditions wereused in the examples.

General Experimental Conditions:

The following mixture was initially prepared:

-   1) 20 ml acetonitrile solvent, or 20 ml acetonitrile +0.5 ml    adiponitrile (1.5 equivalents relative to the CoBr₂), or 20 ml    acetonitrile+MVK (1.5 equivalents relative to the CoBr₂)—methyl    vinyl ketone (MVK) is stable under the operating conditions.    -   Powdered Zn: 50 mmol (3.3 eq/ArX)    -   CF₃COOH: 0.0125 to 0.025M    -   PhBr(Ar′X′): 0.10 eq/ArX    -   CoBr₂: 0.10 eq/ArX    -   ZnBr₂: 0.10 eq/ArX.    -   Once the release of Ar′H was over, in general ¼ of an hour after        the above mixture was produced, the substrate ArX was added in        an amount equal to 15 mmol.-   2) ArBr: 15 mmol    -   Reaction:        FG—Ar—X→FG—Ar—Zn—X    -   where FG represents the substituent under investigation of the        aromatic.

The following nonlimiting examples illustrate the invention.

EXAMPLE 1 Nature of the Solvent

In solvent: 20 ml CH₃CN

FG X % ArH % ArAr % ArX remaining % ArZnX p-OCH₃ Br 10 4 9 78 p-C₂H₅OCOBr 10 17 0 73 m-CF₃ Br 6 10 0 84

In solvent: 20 ml CH₃CN+1.5 eq/CoBr₂ adiponitrile

FG X % ArH % ArAr % ArX remaining % ArZnX p-OCH₃ Br 16 13 0 71 p-C₂H₅OCOBr 11 12 0 76 m-CF₃ Br 12 3 0 80 p-CN Br 3 2 0 95

In solvent: 20 ml CH₃CN+1.5 eq/CoBr₂ MVK

FG X % ArH % ArAr % ArX remaining % ArZnX p-OCH₃ Br 14 34 0 52 p-C₂H₅OCOBr 7 8 0 85 p-CN Br 5 0 0 95

The results obtained from these various solvents vary from one speciesto another; it was therefore chosen to work in a 20 ml CH₃CN+1.5eq/CoBr₂ adiponitrile mixture.

EXAMPLE 2 Nature of the Halide Linked to the Zinc

With ZnBr₂:

% ArX FG X % ArH % ArAr remaining % ArZnX p-OCN Br 0 0 0 100 p-CH₃ Br 920 71

With ZnCl₂:

% ArX FG X % ArH % ArAr remaining % ArZnX p-OCN Br 0 0 0 100

With Zn(CH₂SO₃)₂:

% ArX FG X % ArH % ArAr remaining % ArZnX p-CH₃ Br 50 3 47

EXAMPLE 3 Moment of Introduction of the Zinc Salt (Here ZnBr₂)

In solvent: 20 ml CH₃CN+1.5 eq/CoBr₂ adiponitrile ZnBr₂ in the firststep

FG X % ArH % ArAr % ArX remaining % ArZnX p-OCH₃ Br 16 13 0 71 m-CF₃ Br12  3 0 80 p-COCH₃ Br 15 34 0 52 p-C₂H₅OCO Br 11 12 0 76

In solvent: 20 ml CH₃CN+1.5 eq/CoBr₂ adiponitrile ZnBr₂ in the secondstep

FG X % ArH % ArAr % ArX remaining % ArZnX p-OCH₃ Br 11 0 0 89 p-C₂H₅OCOBr 13 9 0 76 p-COCH₃ Br 15 34 0 52

The results obtained are substantially the same as those obtainedaccording to the usual procedure.

EXAMPLE 4 Nature of the Halide Linked to the Zinc

Either ZnBr₂ or ZnCl₂ is used, the results are the same: in the cases ofp-BrPhCN, 100% p-BrZnPhCN was obtained in both cases.

EXAMPLE 5 Nature of the Activant for the Powdered Zinc

In solvent: 20 ml CH₃CN+1.5 eq/CoBr₂ adiponitrile Activant: CF₃COOH

FG X % ArH % ArAr % ArX remaining % ArZnX p-OCH₃ Br 16 13 0 71 p-C₂H₅OCOBr 11 12 0 76

In solvent: 20 ml CH₃CN+1.5 eq/CoBr₂ adiponitrile Activant: I₂

FG X % ArH % ArAr % ArX remaining % ArZnX p-OCH₃ Br 12 0 0 88 p-C₂H₅OCOBr 7 19 0 75

In solvent: 20 ml CH₃CN+1.5 eq/CoBr₂ adiponitrile Activant: acetic acid

FG X % ArH % ArAr % ArX remaining % ArZnX p-OCH₃ Br 22 0 0 77 p-C₂H₅OCOBr 16 14 0 70

If the activant is I₂, the zinc derivative yields are improved.

EXAMPLE 6 Replacement of PhBr with Other Aromatic Halides in the FirstPhase of the Reaction

Whether Ar′X′, p-BrPhCOOEt, p-BrPhCN, m-BrPhCF₃, o-BrPhCN, or3-bromopyridine was used, results identical to those obtained with PhBrwere obtained. All these halides were converted into PhH, except in thecase of o-BrPhCN, which was partly converted into o-BrZnPhCN.

-   1) Choice of aromatic halide (Ar′Br)    -   Conditions: CH₃CN (20 ml), adiponitrile (0.5 ml), CoBr₂ (0.1        eq), ZnBr₂ (0.1 eq), CF₃COOH (0.0125 to 0.025M), powdered zinc        (3.3 eq), Ar′Br (0.1 eq), addition of 15 mmol of ArBr (1 eq)        when all the Ar′Br has been consumed. ArBr is p-BrPhOCH₃. The        following Ar′X compounds were tested one after another:        p-BrPhCO₂Et, p-BrPhCN, m-BrPhCF₃, o-BrPhCN, 3 BrPyridine.    -   The results obtained (p-BrZnPhOCH₃ yields from 65 to 72%) are        similar to those obtained with PhBr. All the Ar′Br compounds        were converted into ArH, except for o-BrPhCN, which was partly        converted into o-BrZnPhCN.-   2) Influence of the Ar′Br/CoBr₂ ratio    -   The operating conditions were the same as those of 1), with ArBr        being p-BrPhOCH₃ and Ar′X′ being PhBr. Three Ar′X′/CoBr₂ ratios        were examined experimentally.    -   The Ar′Br/CoBr₂ ratio of ½[(0.05 eq)/(0.1 eq)] gave the same        result as with a ratio of 1 [Ar′X=CoBr₂=0.1 eq], namely a        p-BrZnPhOCH₃ yield ranging from 68 to 70%.    -   A ratio of 2 [(0.2 eq)/0.1 eq)] gave the same result. In this        case however, it was established that about 50% of the PhBr was        converted into PhZnBr.

EXAMPLE 7 Influence of the Presence of the Pyridine

-   1) Same conditions as those of example 6-1 with, as solvent, the    CH₃CN/pyridine (20 ml/2.5 ml) mixture, without adiponitrile.    -   With ArBr being p-BrPhOCH₃ and Ar′X′ being PhBr, it was observed        that the reaction was greatly slowed down.-   2) Same conditions as 1), but with no PhBr.    -   Starting from p-BrPhOCH₃, practically no p-BrZnPhOCH₃ was        obtained in 24 H, whereas in the absence of pyridine the        reactions lasted from 15 to 20 min.-   3) Same conditions as 2) with ArBr=p-BrPhCO₂Et.    -   60% ArBr converted into p-BrZnPhCO₂Et in 24 H. Thus, the        presence of pyridine greatly slows down the formation of        organozinc compounds whose ring is rich in electrons.

EXAMPLE 8 Study of the Various Substrates

The following working conditions were chosen:

-   1) Solvent: 20 ml acetonitrile+0.5 ml adiponitrile    -   Powdered zinc: 50 mmol (3.3 eq/Arx)    -   CF₃COOH: (.0.0125 to 0.025M)    -   PhBr(Ar′X′): 0.10 eq/ArX    -   CoBr₂: 0.10 eq/ArX    -   ZnBr₂: 0.10 eq/ArX.-   2) ArBr: 15 mmol    -   The reactions were carried out at room temperature. The results        obtained were the following:

% ArX FG X % ArH % ArAr remaining % ArZnX p-OCH₃ Br 16 13 0 71 m-OCH₃ Br7 23 0 70 o-OCH₃ Br 6 7 0 87 p-CH₃ Br 9 20 0 71 p-C₂H₅OCO Br 11 12 0 76m-CF₃ Br 12 3 0 80 p-Cl Br 6 5 0 89 p-F Br 9 21 0 70 p-COCH₃ Br 15 34 052 p-CN Br 3 2 0 95 m-CN Br 4 0 0 96 o-CN Br 0 0 0 100 3-BromothiopheneBr 29 8 7 55 2-Bromopyridine Br 0 0 100 p-CH₃OCO Cl 23 0 71 6 p-OCH₃ I 83 0 88 p-C₂H₅OCO I 14 11 0 75 X—(CH₂)₃CO₂C₂H₅ Br 43 0 45 12 X—(CH₂)₃CNBr 0 0 100 X—Ph—SO₂ Cl 23 0 37 41 p-CO₂CH₃ Cl 23 0 71 6 p-NH₂ Br 52 0 840 *CoBr₂: 0.20 eq/ArX; ZnBr₂: 0.20 eq/ArX.

EXAMPLE 9 Split Addition of CoBr₂

Same conditions as in example 6 but without Ar′Br and without ArBr andCoBr₂=0.01 eq. The mixture was left for 30 min, then 0.09 eq of CoBr₂and 1 eq of ArBr (p-BrPhCO₂Et) were added.

A p-BrZnPhCO₂Et yield of 60% (reaction yield) was obtained.

EXAMPLE 10 Two-step Reactions

Identical conditions to example 6, but in two steps:

-   1^(st) step: no ArBr and no ZnBr₂-   2^(nd) step: after 10 to 30 minutes, ZnBr₂ (0.1 eq) and ArBr (1 eq)    were added.

Results:

ArBr % ArH % Ar—Ar % ArZnX p-BrPhCO₂Et 13 8 76 p-BrPhCOCH₃ 14 12 74p-BrPhOCH₃ 11 0 89 p-BrPhCH₃ 14 19 67

Results substantially the same as those obtained according to thestandard procedure, except with p-BrPhCOCH₃ where the yield is markedlyincreased (74% of ArZnX in 10 minutes), but at 20° C. this zinc compounddecomposes and is progressively converted into Ar—Ar.

EXAMPLE 11 Influence of the Temperature

Conditions identical to example 6, but the reactions were carried out at0° C. and without adiponitrile.

% ArX Time ArBr % ArH % Ar—Ar remaining % ArZnX (min) p-BrPhCHO 9 44 2323 80 p-BrPhCOCH₃ 8 23 10 59 25

In both cases, progression toward Ar—Ar when the temperature increases.

1. A process for the synthesis of aryl organozinc compounds fromareaction mixture comprising a metallic zinc and an aryl halide of theformula:ArX wherein Ar is an aromatic residue and X is a halogen heavier thanfluorine, said process comprising the step of using cobalt as catalyst.2. The process as claimed in claim 1, wherein the cobalt is introducedinto the reaction mixture in the cobaltous state.
 3. The process asclaimed in claim 1, wherein the cobalt is weakly coordinated.
 4. Theprocess as claimed in claim 1, wherein the synthesis is carried out inthe presence of an adjuvant aromatic halide of the formula:Ar′X′ wherein X′ represents a halogen heavier than fluorine, and Ar′represents an aromatic derivitive whose ring carrying the halogen X′ isless electron-rich than the radical Ar.
 5. The process as claimed inclaim 4, wherein the the aromatic of formula Ar′X′ is present in acontent, expressed in moles per liter, is at most equal to the cobaltconcentration in the reaction mixture.
 6. The process as claimed in 1,wherein the reaction mixture furthermore includes an acid soluble in themixture, or molecular iodine.
 7. The process as claimed in claim 1,wherein the substrate ArX is added last.
 8. The process as claimed inclaim 1, wherein the halide X of ArX is bromine or iodine,advantageously bromine.
 9. A composition forming a reactant that can beused to carry out the synthesis of organozinc compounds, comprising acobalt salt, a zinc salt, a polar aprotic solvent and elemental zinc individed form, the elemental zinc being in solid form, the other elementsbeing in a form dissolved in the solvent.
 10. The composition as claimedin claim 9, further comprising an acid or molecular iodine.